Back to results

Population Pharmacokinetics of Edoxaban in Chinese Patients With Non-Valvular Atrial Fibrillation

Primary Purpose

Non-Valvular Atrial Fibrillation

Status

Recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Edoxaban

About this trial

This is an interventional other trial for Non-Valvular Atrial Fibrillation focused on measuring Edoxaban, Population Pharmacokinetics, Non-Valvular Atrial Fibrillation

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female NVAF patients, who need anticoagulant therapy at least 3 months
Age ≥20 years,
Creatinine clearance rate ≥ 15 ml/min
Sign a written informed consent form (ICF) for participating in the study
No simultaneous participation in any interventional study

Exclusion Criteria:

Patients with the Valve replacement
Patients with valvular atrial fibrillation
Mild and severe anemia patients
CrCl<15ml/min
Patients on dialysis, risk of bleeding, taking antiplatelet drugs, or taking other anticoagulants
Contraindicated to Edoxaban.
Life expectancy < 6 months.
Hypertension defined as systolic and/or diastolic blood pressure > 95th age percentile or poorly controlled hypertension
Hepatic disease which is associated either: with coagulopathy leading to a clinically relevant bleeding risk, or alanine transaminase (ALT) > 5x upper level of normal (ULN), or total bilirubin > 2x ULN with direct bilirubin > 20% of the total.
Active bleeding or high risk for bleeding contraindicating anticoagulant therapy. For example：
- a history of intracranial, intraocular, intraspinal, retroperitoneal, or traumatic intra-articular bleeding
- gastrointestinal bleeding during the prior year
- peptic ulcer within the previous 90 days
- surgery or injury requiring hospitalization within the previous 30 days
- hemoglobin <9 g/dl or a platelet count <50×109/L
- active bleeding at registration
- any procedure associated with bleeding planned to occur during the treatment period
Urine pregnancy test positive if female
Inability to cooperate with the study procedures
Participation in a study with an investigational drug or medical device within 30 days prior to screening
Additional exclusion criteria included, but were not limited to:
- cerebral infarction or transient ischemic attack within the past 30 days
- comorbid rheumatic valvular disease
- comorbid infective endocarditis or atrial myxoma
- evidence of thrombus in the left ventricle or atrium, or hereditary tendency for thrombus formation scheduled electrical or pharmacological defibrillation during the treatment period
- acute myocardial infarction, or unstable angina
- a diagnosis of active malignant tumor or cancer treatment within the past 5 years
- previous treatment with Edoxaban

Sites / Locations

Fuwai Hospital, Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Edoxaban treatment

Arm Description

Outcomes

Primary Outcome Measures

population pharmacokinetic evaluation

Patients enrolled will be back to center for visit at scheduled timepoint. Blood sample for PopPK study was collected. Edoxaban concentrations in patient plasma will be determined, which will be analysed and compared with ENGAGE PopPK model.

pharmacokinetic evaluation

Patients enrolled will be back to center for visit at scheduled timepoint. Blood for pharmacodynamic sample will be collected for Anti-FXa activity determination.

Secondary Outcome Measures

safety evaluation

Patients enrolled will be back to center for visit at scheduled timepoint. Adverse even will be recorded. The investigator will determine whether the patient is suitable to go on with the study.

Full Information

NCT ID

NCT05320627

First Posted

April 2, 2022

Last Updated

June 14, 2022

Sponsor

China National Center for Cardiovascular Diseases

Collaborators

Chinese Academy of Medical Sciences, Fuwai Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05320627

Brief Title

Population Pharmacokinetics of Edoxaban in Chinese Patients With Non-Valvular Atrial Fibrillation

Official Title

Population Pharmacokinetics of Edoxaban in Chinese Patients With Non-Valvular Atrial Fibrillation

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 30, 2022 (Actual)

Primary Completion Date

February 17, 2024 (Anticipated)

Study Completion Date

December 17, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

China National Center for Cardiovascular Diseases

Collaborators

Chinese Academy of Medical Sciences, Fuwai Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

Based on the population pharmacokinetic data of Chinese patients with atrial fibrillation, the study will evaluate the suitability of the ENGAGE Population Pharmacokinetics model of edoxaban in patients with atrial fibrillation in China, and build a predictive dose model of edoxaban that meets the characteristics of Chinese people. It can provide perfect individualized dosing plan improves clinical efficacy and reduces adverse drug reactions.

Detailed Description

This is an open label study. Male or female patients with non-valvular atrial fibrillation (NVAF) with age ≥20 years, and meeting the indications of edoxaban are potentially eligible for the study. Patients receive Edoxaban 15mg、30mg or 60mg according to the criteria as following: Patients with severe renal insufficiency (15ml/min ≤ CrCl <30ml/min), 15mg quaque die (QD) Patients with normal or mild renal insufficiency (CrCl ≥50ml/min), 60mg QD Patients with moderate renal insufficiency (30ml/min ≤ CrCl <50ml/min), weight ≤60kg or combined use of P-gp inhibitors (such as dronedarone，ketoconazole, erythromycin, etc), 30mg QD. Patients will receive clinical evaluation at screening period, 4 weeks、8 weeks and 12 weeks after administration with Edoxaban. The following clinical evaluation items were included: body weight, vital signs (blood pressure and heart rate), CHADS2-VAS score, concomitant medication, ECG and echocardiogram, laboratory examination, safety evaluation (thromboembolic events, bleeding events, death) during treatment. Additional blood samples are collected for pharmacokinetic evaluation at screening period, pre-dose, 2±1h and 6±1h after administration at 4-, 8-, and 12-week visit, and for pharmacodynamic evaluation (FXa) at screening period, pre-dose after administration at 4-, 8-, 12-week visit. The population pharmacokinetics of Edoxaban in Chinese patients with non-valvular atrial fibrillation will be determined after 12weeks clinical observation. The ENGAGE PopPK model suitable in Chinese Patients with Non-Valvular Atrial Fibrillation will be established. Safety outcomes (thromboembolic events, bleeding events, death) will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Valvular Atrial Fibrillation

Keywords

Edoxaban, Population Pharmacokinetics, Non-Valvular Atrial Fibrillation

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Edoxaban treatment

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Edoxaban

Intervention Description

Eligible patients will receive Edoxaban tablet once a day for 12 weeks

Primary Outcome Measure Information:

Title

population pharmacokinetic evaluation

Description

Time Frame

at the 4th, 8th and 12th week

Title

pharmacokinetic evaluation

Description

Patients enrolled will be back to center for visit at scheduled timepoint. Blood for pharmacodynamic sample will be collected for Anti-FXa activity determination.

Time Frame

at the 4th, 8th and 12th week

Secondary Outcome Measure Information:

Title

safety evaluation

Description

Patients enrolled will be back to center for visit at scheduled timepoint. Adverse even will be recorded. The investigator will determine whether the patient is suitable to go on with the study.

Time Frame

at the 4th, 8th and 12th week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female NVAF patients, who need anticoagulant therapy at least 3 months Age ≥20 years, Creatinine clearance rate ≥ 15 ml/min Sign a written informed consent form (ICF) for participating in the study No simultaneous participation in any interventional study Exclusion Criteria: Patients with the Valve replacement Patients with valvular atrial fibrillation Mild and severe anemia patients CrCl<15ml/min Patients on dialysis, risk of bleeding, taking antiplatelet drugs, or taking other anticoagulants Contraindicated to Edoxaban. Life expectancy < 6 months. Hypertension defined as systolic and/or diastolic blood pressure > 95th age percentile or poorly controlled hypertension Hepatic disease which is associated either: with coagulopathy leading to a clinically relevant bleeding risk, or alanine transaminase (ALT) > 5x upper level of normal (ULN), or total bilirubin > 2x ULN with direct bilirubin > 20% of the total. Active bleeding or high risk for bleeding contraindicating anticoagulant therapy. For example： a history of intracranial, intraocular, intraspinal, retroperitoneal, or traumatic intra-articular bleeding gastrointestinal bleeding during the prior year peptic ulcer within the previous 90 days surgery or injury requiring hospitalization within the previous 30 days hemoglobin <9 g/dl or a platelet count <50×109/L active bleeding at registration any procedure associated with bleeding planned to occur during the treatment period Urine pregnancy test positive if female Inability to cooperate with the study procedures Participation in a study with an investigational drug or medical device within 30 days prior to screening Additional exclusion criteria included, but were not limited to: cerebral infarction or transient ischemic attack within the past 30 days comorbid rheumatic valvular disease comorbid infective endocarditis or atrial myxoma evidence of thrombus in the left ventricle or atrium, or hereditary tendency for thrombus formation scheduled electrical or pharmacological defibrillation during the treatment period acute myocardial infarction, or unstable angina a diagnosis of active malignant tumor or cancer treatment within the past 5 years previous treatment with Edoxaban

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lei Tian

Phone

+861088398547

tianlei0807@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Juanjuan Jiang

Phone

+8613466378762

jiangjuanjuan_80@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lu Hua, 1

Organizational Affiliation

Chinese Academy of Medical Sciences, Fuwai Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Lei Tian, 2

Organizational Affiliation

Chinese Academy of Medical Sciences, Fuwai Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fuwai Hospital, Chinese Academy of Medical Sciences

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100037

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hua Lu, PhD

Phone

86-10-88396873

ethannan@126.com

First Name & Middle Initial & Last Name & Degree

Tian Lei, PhD

Phone

86-10-88398547

tianlei0807@163.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Population Pharmacokinetics of Edoxaban in Chinese Patients With Non-Valvular Atrial Fibrillation

We'll reach out to this number within 24 hrs